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Article
Original Article
Exp Neurobiol 2021; 30(2): 120-143
Published online April 30, 2021
https://doi.org/10.5607/en21004
© The Korean Society for Brain and Neural Sciences
Tumor Spheroids of an Aggressive Form of Central Neurocytoma Have Transit-Amplifying Progenitor Characteristics with Enhanced EGFR and Tumor Stem Cell Signaling
Hye Young Shin1, Kyung-Seok Han2†, Hyung Woo Park1†, Yun Hwa Hong3†, Yona Kim1†, Hyo Eun Moon1, Kwang Woo Park1, Hye Ran Park1, C. Justin Lee2, Kiyoung Lee1, Sang Jeong Kim3, Man Seung Heo4, Sung-Hye Park5, Dong Gyu Kim1 and Sun Ha Paek1,6,7*
1Department of Neurosurgery, Seoul National University College of Medicine, Seoul 03082, 2Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, 3Department of Neurophysiology, Seoul National University College of Medicine, Seoul 03082, 4Smart Healthcare Medical Device Research Center, Samsung Medical Center, Seoul 06351, 5Department of Pathology, Seoul National University College of Medicine, Seoul 03082, 6Ischemic/Hypoxic Disease Institute, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03082, 7Clinical Research Institute, Seoul National University Hospital, Seoul 03082, Korea
Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-2072-2350, FAX: 82-2-744-8459
e-mail: paeksh@snu.ac.kr
†These authors contributed equally to this article.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as
Graphical Abstract
Keywords: Central neurocytoma, Tumor spheroids, Subventricular zone, Neural stem cell, Transit-amplifying cells, Radial glia cells, Gene Set Enrichment Analysis
